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International Journal of Molecular... Jan 2023Fibrous dysplasia (FD) is a rare, non-inherited bone disease occurring following a somatic gain-of-function R201 missense mutation of the ( gene. The spectrum of the... (Review)
Review
Fibrous dysplasia (FD) is a rare, non-inherited bone disease occurring following a somatic gain-of-function R201 missense mutation of the ( gene. The spectrum of the disease ranges from a single FD lesion to a combination with extraskeletal features; an amalgamation with café-au-lait skin hyperpigmentation, precocious puberty, and other endocrinopathies defines McCune-Albright Syndrome (MAS). Pain in FD/MAS represents one of the most prominent aspects of the disease and one of the most challenging to treat-an outcome driven by (i) the heterogeneous nature of FD/MAS, (ii) the variable presentation of pain phenotypes (i.e., craniofacial vs. musculoskeletal pain), (iii) a lack of studies probing pain mechanisms, and (iv) a lack of rigorously validated analgesic strategies in FD/MAS. At present, a range of pharmacotherapies are prescribed to patients with FD/MAS to mitigate skeletal disease activity, as well as pain. We analyze evidence guiding the current use of bisphosphonates, denosumab, and other therapies in FD/MAS, and also discuss the potential underlying pharmacological mechanisms by which pain relief may be achieved. Furthermore, we highlight the range of presentation of pain in individual cases of FD/MAS to further describe the difficulties associated with employing effective pain treatment in FD/MAS. Potential next steps toward identifying and validating effective pain treatments in FD/MAS are discussed, such as employing randomized control trials and probing new pain pathways in this rare bone disease.
Topics: Humans; Fibrous Dysplasia, Polyostotic; Endocrine System Diseases; Bone and Bones; Diphosphonates; Musculoskeletal Pain
PubMed: 36768871
DOI: 10.3390/ijms24032550 -
Current Osteoporosis Reports Oct 2016Fibrous dysplasia (FD) is an uncommon and debilitating skeletal disorder resulting in fractures, deformity, functional impairment, and pain. It arises from post-zygotic... (Review)
Review
Fibrous dysplasia (FD) is an uncommon and debilitating skeletal disorder resulting in fractures, deformity, functional impairment, and pain. It arises from post-zygotic somatic activating mutations in GNAS, in the cAMP-regulating transcript α-subunit, Gsα. Constitutive Gs signaling results in activation of adenylyl cyclase and dysregulated cAMP production. In the skeleton, this leads to the development of FD lesions with abnormal bone matrix, trabeculae, and collagen, produced by undifferentiated mesenchymal cells. FD may occur in isolation or in combination with extraskeletal manifestations, including hyperfunctioning endocrinopathies and café-au-lait macules, termed McCune-Albright syndrome (MAS). This review summarizes current clinical and translational perspectives in FD/MAS, with an emphasis on FD pathogenesis, natural history, pre-clinical and clinical investigation, and future directions.
Topics: Animals; Bone Density Conservation Agents; Bone and Bones; Chromogranins; Disease Models, Animal; Fibroblast Growth Factor-23; Fibrous Dysplasia of Bone; Fibrous Dysplasia, Polyostotic; GTP-Binding Protein alpha Subunits, Gs; Humans; Pain Management; Translational Research, Biomedical
PubMed: 27492469
DOI: 10.1007/s11914-016-0317-0 -
Clinical Journal of Oncology Nursing Oct 2017About 85% of patients with multiple myeloma develop bone disease. In these patients, lytic bone lesions can cause fractures, poor circulation, blood clots, pain, poor...
BACKGROUND
About 85% of patients with multiple myeloma develop bone disease. In these patients, lytic bone lesions can cause fractures, poor circulation, blood clots, pain, poor mobility, and decreased quality of life. .
OBJECTIVES
This article presents consensus statements to guide nurses in the assessment and management of bone disease, pain, and mobility in patients with multiple myeloma at varying points in their disease trajectory. .
METHODS
Members of the International Myeloma Foundation Nurse Leadership Board reviewed previously provided recommendations, current recommendations based on literature review, and evidence-based grading. .
FINDINGS
Oncology nurses play a key role in maximizing bone health, minimizing skeletal injury, maximizing pain control, and improving quality of life in patients by enhancing patient mobility and safety. Clinician assessment accompanied by effective interventions reduces patient injury and optimizes functioning in patients with multiple myeloma.
Topics: Bone and Bones; Evidence-Based Medicine; Humans; Movement; Multiple Myeloma; Oncology Nursing; Pain
PubMed: 28945729
DOI: 10.1188/17.CJON.S5.47-59 -
International Journal of Molecular... Feb 2018Osteoarthritis (OA) is the most prevalent joint disease in older people and is characterized by the progressive destruction of articular cartilage, synovial... (Review)
Review
Osteoarthritis (OA) is the most prevalent joint disease in older people and is characterized by the progressive destruction of articular cartilage, synovial inflammation, changes in subchondral bone and peri-articular muscle, and pain. Because our understanding of the aetiopathogenesis of OA remains incomplete, we haven't discovered a cure for OA yet. This review appraises novel therapeutics based on recent progress in our understanding of the molecular pathogenesis of OA, including pro-inflammatory and pro-catabolic mediators and the relevant signalling mechanisms. The changes in subchondral bone and peri-articular muscle accompanying cartilage damage are also reviewed.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Bone Remodeling; Bone and Bones; Cartilage, Articular; Gene Expression Regulation; Humans; Molecular Targeted Therapy; Muscle, Skeletal; Osteoarthritis; Signal Transduction
PubMed: 29495538
DOI: 10.3390/ijms19030674 -
Frontiers in Bioscience (Scholar... Jan 2013Bone defects that cannot "heal spontaneously during life" will become an ever greater health problem as populations age. Harvesting autografts has several drawbacks,... (Review)
Review
Bone defects that cannot "heal spontaneously during life" will become an ever greater health problem as populations age. Harvesting autografts has several drawbacks, such as pain and morbidity at both donor and acceptor sites, the limited quantity of material available, and frequently its inappropriate shape. Researchers have therefore developed alternative strategies that involve biomaterials to fill bone defects. These biomaterials must be biocompatible and interact with the surrounding bone tissue to allow their colonization by bone cells and blood vessels. The latest generation biomaterials are not inert; they control cell responses like adhesion, proliferation and differentiation. These biomaterials are called biomimetic materials. This review focuses on the development of third generation materials. We first briefly describe the bone tissue with its cells and matrix, and then how bone cells interact with the extracellular matrix. The next section covers the materials currently used to repair bone defects. Finally, we describe the strategies employed to modify the surface of materials, such as coating with hydroxyapatite and grafting biomolecules.
Topics: Animals; Biocompatible Materials; Biomimetic Materials; Bone Regeneration; Bone Substitutes; Bone and Bones; Humans
PubMed: 23277057
DOI: 10.2741/s378 -
Frontiers in Endocrinology 2022Osteoarthritis pain is often thought of as a pain driven by nerves that innervate the soft tissues of the joint, but there is emerging evidence for a role for nerves... (Review)
Review
Osteoarthritis pain is often thought of as a pain driven by nerves that innervate the soft tissues of the joint, but there is emerging evidence for a role for nerves that innervate the underlying bone. In this mini review we cite evidence that subchondral bone lesions are associated with pain in osteoarthritis. We explore recent studies that provide evidence that sensory neurons that innervate bone are nociceptors that signal pain and can be sensitized in osteoarthritis. Finally, we describe neuronal remodeling of sensory and sympathetic nerves in bone and discuss how these processes can contribute to osteoarthritis pain.
Topics: Humans; Pain; Osteoarthritis; Bone and Bones; Sensory Receptor Cells; Bone Diseases
PubMed: 36605943
DOI: 10.3389/fendo.2022.1047943 -
Biochimica Et Biophysica Acta Oct 2015Solid and hematologic cancer colonized bone produces a number of pathologies. One of the most common complications is bone pain. Cancer-associated bone pain (CABP) is a... (Review)
Review
Solid and hematologic cancer colonized bone produces a number of pathologies. One of the most common complications is bone pain. Cancer-associated bone pain (CABP) is a major cause of increased morbidity and diminishes the quality of life and affects survival. Current treatments do not satisfactorily control CABP and can elicit adverse effects. Thus, new therapeutic interventions are needed to manage CABP. However, the mechanisms responsible for CABP are poorly understood. The observation that specific osteoclast inhibitors can reduce CABP in patients indicates a critical role of osteoclasts in the pathophysiology of CABP. Osteoclasts create an acidic extracellular microenvironment by secretion of protons via vacuolar proton pumps during bone resorption. In addition, bone-colonized cancer cells also release protons and lactate via plasma membrane pH regulators to avoid intracellular acidification resulting from increased aerobic glycolysis known as the Warburg effect. Since acidosis is algogenic for sensory neurons and bone is densely innervated by sensory neurons that express acid-sensing nociceptors, the acidic bone microenvironments can evoke CABP. Understanding of the mechanism by which the acidic extracellular microenvironment is created in cancer-colonized bone and the expression and function of the acid-sensing nociceptors are regulated should facilitate the development of novel approaches for management of CABP. Here, the contribution of the acidic microenvironment created in cancer-colonized bone to elicitation of CABP and potential therapeutic implications of blocking the development and recognition of acidic microenvironment will be described. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.
Topics: Acid Sensing Ion Channels; Analgesics; Bone Neoplasms; Bone Resorption; Bone and Bones; Gene Expression Regulation, Neoplastic; Humans; Hydrogen-Ion Concentration; Lactic Acid; Monocarboxylic Acid Transporters; Osteoclasts; Osteosarcoma; Pain; Protons; TRPV Cation Channels; Tumor Microenvironment
PubMed: 25687976
DOI: 10.1016/j.bbamem.2015.02.004 -
Brain Research Reviews Apr 2009Non-malignant musculoskeletal pain is the most common clinical symptom that causes patients to seek medical attention and is a major cause of disability in the world.... (Review)
Review
Non-malignant musculoskeletal pain is the most common clinical symptom that causes patients to seek medical attention and is a major cause of disability in the world. Musculoskeletal pain can arise from a variety of common conditions including osteoarthritis, rheumatoid arthritis, osteoporosis, surgery, low back pain and bone fracture. A major problem in designing new therapies to treat musculoskeletal pain is that the underlying mechanisms driving musculoskeletal pain are not well understood. This lack of knowledge is largely due to the scarcity of animal models that closely mirror the human condition which would allow the development of a mechanistic understanding and novel therapies to treat this pain. To begin to develop a mechanism-based understanding of the factors involved in generating musculoskeletal pain, in this review we present recent advances in preclinical models of osteoarthritis, post-surgical pain and bone fracture pain. The models discussed appear to offer an attractive platform for understanding the factors that drive this pain and the preclinical screening of novel therapies to treat musculoskeletal pain. Developing both an understanding of the mechanisms that drive persistent musculoskeletal pain and novel mechanism-based therapies to treat these unique pain states would address a major unmet clinical need and have significant clinical, economic and societal benefits.
Topics: Animals; Arthralgia; Bone and Bones; Disease Models, Animal; Fractures, Bone; Humans; Hyperalgesia; Inflammation; Mice; Musculoskeletal Diseases; Osteoarthritis; Pain, Postoperative; Rats; Thoracotomy
PubMed: 19166876
DOI: 10.1016/j.brainresrev.2008.12.012 -
The Journal of Pain Nov 2021Skeletal diseases and their surgical treatment induce severe pain. The innervation density of bone potentially explains the severe pain reported. Animal studies... (Observational Study)
Observational Study
Skeletal diseases and their surgical treatment induce severe pain. The innervation density of bone potentially explains the severe pain reported. Animal studies concluded that sensory myelinated A∂-fibers and unmyelinated C-fibers are mainly responsible for conducting bone pain, and that the innervation density of these nerve fibers was highest in periosteum. However, literature regarding sensory innervation of human bone is scarce. This observational study aimed to quantify sensory nerve fiber density in periosteum, cortical bone, and bone marrow of axial and appendicular human bones using immunohistochemistry and confocal microscopy. Multivariate Poisson regression analysis demonstrated that the total number of sensory and sympathetic nerve fibers was highest in periosteum, followed by bone marrow, and cortical bone for all bones studied. Bone from thoracic vertebral bodies contained most sensory nerve fibers, followed by the upper extremity, lower extremity, and parietal neurocranium. The number of nerve fibers declined with age and did not differ between male and female specimens. Sensory nerve fibers were organized as a branched network throughout the periosteum. The current results provide an explanation for the severe pain accompanying skeletal disease, fracture, or surgery. Further, the results could provide more insight into mechanisms that generate and maintain skeletal pain and might aid in developing new treatment strategies. PERSPECTIVE: This article presents the innervation of human bone and assesses the effect of age, gender, bone compartment and type of bone on innervation density. The presented data provide an explanation for the severity of bone pain arising from skeletal diseases and their surgical treatment.
Topics: Age Factors; Bone Diseases; Bone Marrow; Cortical Bone; Humans; Immunohistochemistry; Musculoskeletal Pain; Periosteum
PubMed: 33964414
DOI: 10.1016/j.jpain.2021.04.006 -
Journal of Orthopaedic Research :... Apr 2021Vitamin C (ascorbic acid), is an important antioxidant that has been applied broadly in the field of orthopaedics. Current research on vitamin C examines the molecule's... (Review)
Review
Vitamin C (ascorbic acid), is an important antioxidant that has been applied broadly in the field of orthopaedics. Current research on vitamin C examines the molecule's role in bone and tendon physiology, as well as joint replacement and Postoperative pain. Most laboratory and human studies associate the use of vitamin C with improved bone health and tendon healing. Recent literature moderately supports the use of vitamin C to improve functional outcomes, decreased postoperative pain, and prevent complex regional pain syndrome following orthopaedic procedures. The perioperative use of vitamin C in patients undergoing joint replacement surgery and anterior cruciate ligament reconstruction is still under investigation. Overall, there is need for high-quality human trials to confirm whether vitamin C can potentiate the outcomes of orthopaedic procedures and to determine optimal dosage and means of administration to maximize its proposed benefits. The purpose of this review was to summarize the application of vitamin C in orthopaedic practices and to identify potential areas for future study.
Topics: Animals; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Antioxidants; Arthroplasty, Replacement; Ascorbic Acid; Bone and Bones; Clinical Trials as Topic; Humans; Orthopedics; Osteoporosis; Pain, Postoperative; Perioperative Period; Randomized Controlled Trials as Topic; Tendons; Treatment Outcome
PubMed: 33300201
DOI: 10.1002/jor.24947